2. Academic Validation
  3. Inducible degradation of lncRNA Sros1 promotes IFN-γ-mediated activation of innate immune responses by stabilizing Stat1 mRNA

Inducible degradation of lncRNA Sros1 promotes IFN-γ-mediated activation of innate immune responses by stabilizing Stat1 mRNA

  • Nat Immunol. 2019 Dec;20(12):1621-1630. doi: 10.1038/s41590-019-0542-7.
Henan Xu 1 2,  Yan Jiang 1,  Xiaoqing Xu 1,  Xiaoping Su 2,  Yang Liu 1,  Yuanwu Ma 3,  Yong Zhao 4,  Zhongyang Shen 5,  Bo Huang 1,  Xuetao Cao 6 7 8
Affiliations

Affiliations

  • 1 Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
  • 2 National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
  • 3 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China.
  • 4 Fuwai Central China Cardiovascular Hospital, Chinese Academy of Medical Sciences, Zhengzhou, China.
  • 5 Tianjin First Center Hospital, Tianjin, China.
  • 6 Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. caoxt@immunol.org.
  • 7 National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China. caoxt@immunol.org.
  • 8 College of Life Sciences, Nankai University, Tianjin, China. caoxt@immunol.org.
PMID: 31740800 DOI: 10.1038/s41590-019-0542-7
Abstract

Interferon-γ (IFN-γ) is essential for the innate immune response to intracellular bacteria. Noncoding RNAs and RNA-binding proteins (RBPs) need to be further considered in studies of regulation of the IFN-γ-activated signaling pathway in macrophages. In the present study, we found that the MicroRNA miR-1 promoted IFN-γ-mediated clearance of Listeria monocytogenes in macrophages by indirectly stabilizing the STAT1 messenger RNA through the degradation of the cytoplasmic long noncoding RNA Sros1. Inducible degradation or genetic loss of Sros1 led to enhanced IFN-γ-dependent activation of the innate immune response. Mechanistically, Sros1 blocked the binding of STAT1 mRNA to the RBP CAPRIN1, which stabilized the STAT1 mRNA and, consequently, promoted IFN-γ-STAT1-mediated innate immunity. These observations shed LIGHT on the complex RNA-RNA regulatory networks involved in cytokine-initiated innate responses in host-pathogen interactions.

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